Tisento Launches with $81 Million and Cyclerion Assets Targeting Genetic Mitochondrial Diseases
July 31, 2023
Rare Daily Staff
Cyclerion Therapeutics and Tisento Therapeutics closed a previously disclosed asset purchase agreement, launching Tisento with an $81 million series A financing to support its development of zagociguat in MELAS and other genetic mitochondrial diseases.
Major Cyclerion shareholders participated in Tisento’s Series A financing, including Invus, Peter Hecht, Polaris, and others. They are joined in the Tisento investor syndicate by Sanofi Ventures, Venrock, J. Wood Capital, and others.
In the transaction, Tisento acquired Cyclerion’s zagociguat and CY3018, a CNS-targeted sGC stimulator in IND-enabling studies. Cyclerion received 10 percent equity ownership in Tisento with anti-dilution protection through $100 million in post-money valuation, as well as the right to purchase additional Tisento equity in the future. The Tisento equity ownership provides Cyclerion shareholders with the opportunity to benefit from future Tisento value creation without further financial or operational obligations for the Tisento assets. In addition, Cyclerion received a $10.4 million cash payment, consisting of an $8 million upfront payment and reimbursement for certain employee and development expenses related to zagociguat and CY3018 for the period between the signing and closing of the transaction. In conjunction with the asset sale, Peter Hecht invested $5 million in Cyclerion.
MELAS is an acronym for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. It belongs to a clinical spectrum of mitochondrial diseases most frequently caused by a mutation in the MT-TL1 gene in mitochondrial DNA. MELAS syndrome begins in childhood, usually between the ages of two and fifteen years, with approximately 75 percent of cases reporting an onset of the disorder before the age of 20 years. Although rare, it is one of the most common types of mitochondrial diseases caused by mutations in the mtDNA, with an estimated prevalence for MELAS spectrum disorders in adults and children of risk of 4.4 in 100,000 people.
MELAS syndrome is a progressive and often early fatal disorder affecting organs and tissues with a high-energy demand, such as the brain and skeletal muscle. Current existing therapies only manage the symptoms and don’t target the underlying cause of the disease.
Zagociguat is a first-in-class, brain-penetrant soluble guanylate cyclase stimulator that modulates the nitric oxide-cyclic guanosine monophosphate pathway, a fundamental cell-signaling pathway, and has shown potential to treat both central nervous system and peripheral symptoms of mitochondrial diseases.
Phase 2a clinical data, generated by Cyclerion, showed rapid improvements in disease-associated biomarkers in patients with MELAS who received zagociguat for 28 days. In the study, zagociguat exhibited an excellent safety profile, exposure in the CNS and throughout the body consistent with once-daily oral dosing, and improvements across key domains of the disease pathophysiology including neuronal function, mitochondrial function, cerebrovascular hemodynamics, and inflammatory processes.
“Tisento is launching with a phase 2b-ready asset, compelling clinical data, an experienced team led by CEO Peter Hecht, committed investors, and an established network of healthcare providers and patient advocates,” said Bryan Roberts, chair of the Board at Tisento and partner at Venrock. “The nitric oxide-cyclic GMP pathway has yielded a number of meaningful approved therapies. We are excited to extend the potential of this mechanism into the central nervous system by advancing the first brain-penetrant sGC stimulators.”
Photo: Bryan Roberts, chair of the Board at Tisento and partner at Venrock
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